This application is the National Phase of International Application PCT/GB00/00979 filed Mar. 16, 2000 which designated the U.S. and that International Application was.
The present invention relates to a stable aqueous dispersion of a halopropynyl compound and to its use in inhibiting the growth of micro organisms such as fungi and algae on or in a medium, especially an industrial medium.
Halopropargyl compounds (hereinafter HPC""s) are well-known fungicides and the most widely used is 3-iodo-2-propynyl-N-n-butylcarbamate (herein after IPBC). IPBC is available commercially in both solid form and as a liquid concentrate in organic solvents.
During the last few years there has been an increasing demand for industrial biocide formulations which contain low levels of volatile organic compounds (hereinafter low VOC) and particularly a demand for wholly aqueous formulations. Hitherto, this has been difficult to achieve in the case of HPC""s such as IPBC because of their low but significant aqueous solubility. Because of this low solubility in water there is a tendency for small particles to dissolve and to be deposited on larger particles. There is, thus, a tendency for the particle size distribution of the aqueous dispersion to change on storage to fewer particles of larger size. This coarsening of the particle size is referred to as xe2x80x9cOstwald ripeningxe2x80x9d as discussed, for example, in xe2x80x9cCrystallisationxe2x80x9d by J. W. Mullin, 3rd edition, published by Butterworth/Heinemann, paperback edition 1997, pages 288 to 290. This Ostwald ripening manifests itself in instability of the aqueous dispersion, especially under adverse storage conditions and results in layering and sedimentation of the HPC.
We have examined a number of dispersants of both the non-ionic and anionic type which are designed for distributing particulate solids in an aqueous medium. None of those examined have resulted in stable aqueous dispersions of the HPC. However, we have now found that one class of dispersant which exhibits weak surface-active properties does result in aqueous dispersions of HPC""s with surprisingly good storage stability especially under freeze/thaw conditions. These dispersants are partially hydrolysed polyvinyl alcohols (hereinafter PHPVA).
According to a first aspect of the present invention there is provided an aqueous dispersion comprising a HPC and a PHPVA.
Preferably, the HPC is a compound of formula 1 
wherein
Y is halogen;
R1 and R2 are each, independently, C1-6-alkyl, C2-6-alkenyl or C3-7-cycloalkyl;
m is from 1 to 6; and
X is an organic moiety linked to the xe2x80x94CR1R2xe2x80x94 group via an oxygen, nitrogen, sulphur or carbon atom.
Preferably, Y is chlorine, bromine and especially iodine. The compound of formula 1 wherein Y is iodine is an iodopropargyl compound (hereinafter IPC).
The organic moiety linked to the xe2x80x94CR1R2xe2x80x94 group via an oxygen, nitrogen, sulphur or carbon atom preferably contains not greater than 20 and especially not greater than 10 carbon atoms.
The compound of formula 1 wherein the organic moiety is linked to the group xe2x80x94CR1R2xe2x80x94 via an oxygen atom is preferably an ether, ester or especially a carbamate.
The compound of formula 1 wherein the organic moiety is linked to the group xe2x80x94CR1R2xe2x80x94 via a nitrogen atom is preferably an amine or amide.
The compound of formula 1 wherein the organic moiety is linked to the group xe2x80x94CR1R2xe2x80x94 via a sulphur atom is preferably a thiane, sulphone or sulphoxide.
The organic moiety can be alkyl, alkenyl, aryl, heteroaryl, aralkyl, cycloalkyl or cycloalkenyl, all of which may be optionally substituted. When the organic moiety is alkyl, it may be linear or branched but is preferably linear.
Optional substituents in the organic moiety are halogen (preferably chlorine, bromine or iodine), C1-6-alkyl and C1-6-alkoxy.
Preferably, R1 and R2 are both hydrogen.
Preferably m is one.
According to a first preferred embodiment of the invention the IPC is a compound of formula 2 
wherein
R is hydrogen, optionally substituted C1-20-alkyl, optionally substituted C2-20-alkenyl, optionally substituted aryl, optionally substituted aralkyl, C3-20-cycloalkyl or C3-20-cycloalkenyl; and
n and p are each, independently, from 1 to 3.
When R is C1-20-alkyl it is preferably C1-8-alkyl or more preferably C1-6-alkyl. The alkyl group may be linear or branched. Examples are methyl, ethyl, propyl , sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, octadecyl and especially n-butyl.
When R is aryl, it is preferably phenyl.
When R is aralkyl, it is preferably 2-phenylether or benzyl.
When R is cycloalkyl, it is preferably C4-7-cycloalkyl, more preferably cyclopropyl or cyclohexyl.
When R is cycloalkenyl, it is preferably cyclohexenyl.
Preferred optional substituent(s) carried by R include halogen (preferably chlorine, bromine or iodine), C1-6-alkyl or C1-6-alkoxy. It is preferred, however, that R is unsubstituted.
Preferably n is one. Preferably p is one.
The IPC""s of formula 2 are disclosed in U.S. Pat. No. 3,923,870; U.S. Pat. No. 4,259,350; U.S. Pat. No. 4,592,773; U.S. Pat. No. 4,616,004; U.S. Pat. No. 4,719,227 and U.S. Pat. No. 4,945,109.
Especially preferred IPC""s of formula 2 are 3-iodo-2-propynyl-N-n-propyl carbamate, 3-iodo-2-propynyl-N-n-butylcarbamate, 3-iodo-2-propynyl-N-n-hexyl carbamate, 3-iodo-2-propynyl-N-cyclohexylcarbamate and 3-iodo-2-propynyl-N-phenyl carbamate.
According to a second aspect of the invention, the IPC is a compound of formula 3
wherein:
R is defined hereinbefore;
R1 and R2 are each, independently, C1-6-alkyl, C2-6-alkenyl, C3-7-cycloalkyl or xe2x80x94CR1R2xe2x80x94 represents (xe2x80x94CH2)txe2x80x94 where t is from 4 to 6; and
R3 to R6 are each, independently, hydrogen, C1-4-alkyl, aryl, xe2x80x94CCI3 or R3 with R5 or R4 with R6 represents xe2x80x94(CH2)qxe2x80x94 where q is from 3 to 5.
The preparation of IPC""s of formula 3 are described in, for example U.S. Pat. No. 4,474,807.
Especially, preferred IPC""s of formula 3 are 2-(3-iodo-2-propynyloxy)-ethyl-N-methylcarbamate, 2-(3-iodo-2-propynyloxy)-ethyl-N-n-butylcarbamate, 2-(3-iodo-2-propynyloxy)-ethyl-N-phenylcarbamate and 2-(3-iodo-2-propynyloxy)-ethyl-N-(4-chlorophenyl)carbamate.
It is especially preferred that the aqueous dispersion contains an IPC of formula 2 and that the IPC of formula 2 is IPBC.
The PHPVA is preferably obtainable from a polyvinyl ester of an organic acid where the organic acid contains from 1 to 6 carbon atoms excluding the carbonyl carbon atom. Typically the PHPVA is obtainable by partial hydrolysis of the polyvinyl ester of the organic ester, for example by saponification using a suitable base such as KOH or NaOH. Thus, the PHPVA contains both hydroxy groups and C1-6-hydrocarbyl-carbonyl radicals. It is preferred that the organic acid is acetic acid whereby the PHPVA is a partially hydrolysed polyvinyl acetate.
Preferably, a 4% aqueous solution of the PHPVA has a viscosity from 2.5 to 42, more preferably from 5 to 27.5 and especially from 7 to 24.5 mPa.s at 20xc2x0 C. as determined, for example, using DIN 53015.
It is also preferred that the degree of hydrolysis of the partially hydrolysed polyvinyl ester of the organic acid is from 71 to 89 (more preferably from 71.6 to 88.7) mole %.
The ester value of the PHPVA is preferably from 80 to 280 mg KOH/gm, more preferably from 130 to 210 mg KOH/gm and especially from 130 to 150 mg KOH/gm. The ester value refers to the number of mg of KOH required for the neutralisation of the acid released by saponification of 1 g of PHPVA
In the case of PHPVA which is derived from polyvinyl acetate, the residual acetyl content is preferably from 7.1 to 22% by weight and especially from 10 to 11.6% by weight.
The amount of HPC in the aqueous dispersion is preferably not less than 1%, more preferably not less than 5% and especially not less than 10% by weight of the total amount of the dispersion. It is also preferred that the amount of HPC is not greater than 60%, more preferably not greater than 50% and especially not greater than 30% by weight based on the total amount of the dispersion.
The amount of PHPVA dispersant in the aqueous formulation depends on the amount of HPC and is preferably from 1 to 10% and especially from 2 to 5% based on the total weight of the dispersion.
The aqueous dispersion may be made by any means known to the art and includes subjecting the HPC to grinding or milling in water in the presence of the PHPVA dispersant to reduce the particle size. Preferably, milling or grinding is continued until the particle size is less than 10xcexc, more preferably less than 5xcexc and especially less than 2xcexc. The particle size of the HPC may be reduced by bead, ball or gravel milling and may be preceded by high-shear mixing in a mixer such as a Silverson mixer.
The aqueous dispersion may contain other adjuvents such as humectants. Preferred humectants have a low vapour pressure at ambient temperatures and therefore a low volatility. Suitable humectants include diols, preferably diols having from 2 to 12 carbon atoms, for example pentane-1,5-diol, ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol and thiodiglycol and oligo- and poly-alkyleneglycols, preferably diethylene glycol, triethylene glycol, polyethylene glycol (preferably with an average Mn less than 1000, more preferably  less than 500) and polypropylene glycol (preferably with an average Mn less than 1000); triols, preferably glycerol and 1,2,6-hexanetriol; mono-C1-4-alkyl ethers of diols, preferably mono-C1-4-alkyl ethers of diols having 2 to 12 carbon atoms, especially 2-methoxyethanol, 2-(2-methoxyethoxy)ethanol, 2-(2-ethoxyethoxy)-ethanol, 2-[2-(2-methoxyethoxy)ethoxy]ethanol, 2-[2-(2-ethoxyethoxy)-ethoxy]-ethanol and ethyleneglycol monoallylether; and urea. More preferably the humectant is ethyleneglycol, propyleneglycol, polyethyleneglycol and especially glycerol.
The amount of humectant in the aqueous formulation is preferably from 1 to 10% and especially from 2 to 7% by weight of the total dispersion. We have found that the presence of a humectant reduces the tendency for the HPC particles to aggregate in the aqueous dispersion under freeze/thaw conditions.
The aqueous dispersion may also contain a compound which gives structure to water and which can inhibit the sedimentation of the HPC. Examples of such compounds are polysaccharides, xanthan gum, sodium magnesium silicate, heteropolysaccharides, alginates, carboxymethyl cellulose, gum arabic and polyacrylic acid. Xanthan gum is preferred. Preferably, the amount of such compounds in the dispersion is from 0.1 to 0.5% and especially from 0.3 to 0.4% based on the total weight of the dispersion. Preferably the aqueous dispersion has a viscocity at 20xc2x0 C. of from 1000 to 4000 cP, more preferably from 1500 to 3500 cP, especially from 1600 to 2500 cP and more especially about 2000 cP as measured at an applied shear rate of 2.3 reciprocal seconds.
Preferably the aqueous dispersion is free from dispersants and/or surfactants other than the PHPVA. We have found that the presence of some additional dispersants and/or surfactants in the aqueous dispersion can cause undesirable crystal growth of the HPC, and therefore an unstable dispersion, during long term storage. It is especially preferred that the aqueous dispersion is free from anionic surfactants/dispersants and non-ionic surfactants/dispersants other than the PHPVA.
Preferably the aqueous dispersion is substantially free from volatile organic compounds. The presence of such compounds is undesirable because there are increasingly stringent environmental regulations requiring formulations to have low VOC content. It is preferred that the aqueous dispersion contains less than 5%, more preferably less than 1% volatile organic compounds.
In an embodiment of the present invention the aqueous dispersion further comprises one or more further antimicrobial compound(s) in addition to the HPC. The presence of further antimicrobial compound(s) can provide a broader spectrum of antimicrobial activity than the HPC alone. Furthermore, the combination of the HPC and further additional antimicrobial compound(s) may provide a synergistic effect.
The further antimicrobial compound or compounds may possess anti-bacterial, anti-fungal, anti-algal or other antimicrobial activity.
Examples of further antimicrobial compounds which may be used, together with the HPC include quatemary ammonium compounds for example, N,N-diethyl-N-dodecyl-N-benzylammonium chloride, N,N-dimethyl-N-octadecyl-N-(dimethylbenzyl)ammonium chloride, N,N-dimethyl-N,N-didecylammonium chloride, N,N-dimethyl-N,N-didodecylammonium chloride; N,N,N-trimethyl-N-tetradecylammonium chloride, N-benzyl-N,N-dimethyl-N-(C12-C18alkyl)ammonium chloride, N-(dichlorobenzyl)-N,-N-dimethyl-N-dodecylammonium chloride, N-hexadecylpyridinium chloride, N-hexadecylpyridinium bromide, N-hexadecyl-N,N,N-trimethylammonium bromide, N-dodecylpyridinium chloride, N-dodecylpyridinium bisulphate, N-benzyl-N-dodecyl-N,N-bis(beta-hydroxy-ethyl)ammonium chloride, N-dodecyl-N-benzyl-N,N-dimethylammonium chloride, N-benzyl-N,N-dimethyl-N-(C12-C18 alkyl)ammonium chloride, N-dodecyl-N,N-dimethyl-N-ethylammonium ethylsulphate, N-dodecyl-N,N-dimethyl-N-(1-naphthylmethyl)ammonium chloride, N-hexadecyl-N,N-dimethyl-N-benzylammonium chloride, N-dodecyl-N,N-dimethyl-N-benzylammonium chloride or 1-(3-chloroallyl)-3,5,7-triaza-1-azonia-adamantane chloride; urea derivatives for example 1,3-bis(hydroxymethyl)-5,5-dimethylhydantoin, bis(hydroxymethyl)urea, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (Diuron), 3-(4-isopropylphenyl)-1,1-dimethylurea, tetrakis(hydroxymethyl)-acetylenediurea, 1-(hydroxymethyl)-5,5-dimethylhydantoin or imidazolidinylurea; amino compounds for example 1,3-bis(2-ethyl-hexyl)-5-methyl-5-aminohexahydro-pyrimidine, hexamethylenetetramine, 1,3-bis(4-aminophenoxy)propane, dodecylamine or 2-[(hydroxymethyl)-amino]ethanol; imidazole derivatives for example 1[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole or 2-(methoxycarbonyl-amino)-benzimidazole (Carbendazim); nitrile compounds for example 2-bromo2-bromomethyl-glutaronitrile, 2-chloro-2-chloro-methylglutaro-nitrile, 1,2-dibromo-2,4-dicyanobutane or 2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile (Chlorothaolnil); thiocyanate derivatives for example methylene(bis)thiocyanate or 2-(thiocyanomethylthio)-benzothiazole; tin compounds or complexes for example tributyltinoxide, chloride, naphthoate, benzoate or 2-hydroxybenzoate; isothiazolin-3-ones, for example 4,5-trimethylene4-isothiazolin-3-one, 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, 2-methylisothiazolin-3-one, 5-chloro-2-methyl-isothiazolin-3-one, benzisothiazolin-3-one; 2-methylbenzisothiazolin-3-one, 2-n-butylbenzisothiazolin-3-one, 2-octylisothiazolin-3-one or 4,5-dichloro-2-octylisothiazolin-3-one; thiazole derivatives for example, 2-(thiocyanomethylthio)-benzthiazole or mercaptobenzthiazole; nitro compounds for example, tris(hydroxymethyl)nitromethane, 5-bromo-5-nitro-1,3-dioxane or 2-bromo-2-nitropropane-1,3-diol (Bronopol); iodine compounds, for example tri-iodo allyl alcohol; aldehydes and aldehyde release agents, for example glutaraldehyde (pentanedial), formaldehyde or glyoxal; amides for example chloracetamide, N,N-bis(hydroxymethyl)chloracetamide, N-hydroxymethyl-chloracetamide or dithio-2,2-bis(benzmethylamide); guanidine derivatives for example poly(hexamethylenebiguanide) or 1,6-hexamethylene-bis[5-(4-chlorophenyl)biguanide]; thiones for example 3,5-dimethyltetrahydro-1,3,5-2H-thiodiazine-2-thione; sulphamides, for example N-dimethyl-Nxe2x80x2-phenyl-(fluorodichloromethylthio)sulphamide (Preventol A4); triazine derivatives for example hexahydrotriazine, 1,3,5-tri-(hydroxyethyl)-1,3,5-hexahydrotriazine, 6-chloro-2,4-diethyl-amino-s-triazine or 4-cyclopropylamino-2-methylthio-6-t-butylamino-s-triazine (Irgarol); oxazolidine and derivatives thereof for example bis-oxazolidine; furan and derivatives thereof for example 2,5-dihydro-2,5-dialkoxy-2,5-dialkylfuran; antimicrobial carboxylic acids and the salts and esters thereof for example sorbic acid and 4-hydroxybenzoic acid and their salts and esters; phenol and derivatives thereof for example 5-chloro-2-(2,4-dichloro-phenoxy)phenol, thio-bis(4-chlorophenol) or 2-phenylphenol; sulphone derivatives for example diiodomethyl-paratolylsulphone, 2,3,5,6-tetrachloro-4-(methylsulphonyl)pyridine or hexachlorodimethylsulphone; imides for example, N-(fluorodichloromethylthio)phthalimide (Preventol A3), N-(trichloromethylthio)phthalimide (Folpet) or N-(trichloromethyl)thio-4-cyclohexene-1,2-dicarboxyimide (Captan); thioamides for example dimethyidithiocarbamate and its metal complexes, ethylenebisdithiocarbamate and its metal complexes, or 2-mercapto-pyridine-N-oxide and its metal complexes and salts (especially the 2:1 zinc complex and the sodium salt); azole fungicides for example hexaconazole, tebuconazole, propiconazole, etaconazole or tetraconazole; strobilurins, for example methyl-(E)-2-[2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxyacrylate (Azoxystrobin), methyl-(E)-methoxyimino[xcex1-(o-tolyloxy)-o-tolyl]acetate, N-methyl-(E)-methoxyimino[2-(2,5-dimethlyphenoxymethyl)phenyl]acetamide, N-methyl-(E)-2-methoxyimino-2-(2-phenoxyphenyl)acetamide (Metominostrobin) or Trifloxystrobin.
The amount of further antimicrobial compound(s) in the aqueous dispersion will depend upon the further antimicrobial compound and the medium on or in which the dispersion will be used to protect against microbial degradation. Preferably the weight ratio of the HPC:further antimicrobial compound(s) is from 10:1 to 1:10, more preferably from 5:1 to 1:5 and especially from 2:1 to 1:2.
The further antimicrobial compound(s) may be added to the aqueous dispersion of the HPC and PHPVA directly or in any convenient form, for example as an emulsion, a micro-emulsion or as a solution, preferably an aqueous solution. When the additional antimicrobial compound is a solid which is insoluble in water it is preferably added to the HPC and PHPVA during milling/grinding to form a co-dispersion with the HPC.
Alternatively, the further antimicrobial compound may be added to the aqueous dispersion of the HPC and PHPVA as an aqueous dispersion.
In a preferred embodiment of the invention the aqueous dispersion comprises a HPC; a PHPVA; and 2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile (Chlorothaolnil), wherein the HPC and PHPVA are as hereinbefore defined. We have found that this dispersion is particularly effective for inhibiting the growth of fungi in or on a medium, particularly an industrial medium and especially in paint films.
In view of the foregoing preferences a preferred aqueous dispersion comprises:
(a) from 1 to 60, more preferably from 10 to 50 parts of IPBC;
(b) from 1 to 10, more preferably from 2 to 5 parts of a partially hydrolysed polyvinylacetate, wherein the degree of hydrolysis is from 71.6 to 88.7 mole %; and
(c) from 0 to 40, more preferably 0 to 10 parts in total of one or more further antimicrobial compound(s) other than IPBC (preferably Chlorothalonil);
(d) from 0 to 10, more preferably 1 to 10 parts humectant (preferably glycerol); and
(e) from 30 to 98 parts water;
wherein all parts are by weight and the sum of the parts (a)+(b)+(c)+(d)+(e)=100.
The aqueous dispersion according to the present invention is used to inhibit the growth of micro-organisms such as fungi and algae in or on a medium, preferably an industrial medium. Examples of industrial media include paint films, wood, leather, adhesives, tarpaulins, cellulose canvas, silicone sealants, metal working fluids, polymer emulsions, cooling waters, lacquers, varnishes, masonary, buildings, geological drilling lubricants and plastics materials such as polyurethanes, polyamines, polyesters, polyacrylonitrile, polyolefins and PVC, particularly plasticised PVC.
According to a second aspect of the present invention there is provided a medium treated with an aqueous dispersion according to the first aspect of the present invention. The medium is preferably an industrial medium as hereinbefore defined.
According to a third aspect of the present invention there is provided a method for inhibiting the growth of micro-organisms on or in a medium comprising adding thereto an aqueous dispersion according to the first aspect of the present invention.
The preferred aqueous dispersions are as hereinbefore described in relation to the first aspect of the invention.